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Deficient angiogenesis in redox-dead Cys17Ser PKARIα knock-in mice

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Article number7920
Number of pages8
JournalNature Communications
Volume6
Issue number1
Early online date10 Aug 2015
DOIs
Accepted/In press24 Jun 2015
E-pub ahead of print10 Aug 2015
Published10 Aug 2015

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King's Authors

Abstract

Angiogenesis is essential for tissue development, wound healing and tissue perfusion, with its dysregulation linked to tumorigenesis, rheumatoid arthritis and heart disease. Here we show that pro-angiogenic stimuli couple to NADPH oxidase-dependent generation of oxidants that catalyse an activating intermolecular-disulphide between regulatory-RIα subunits of protein kinase A (PKA), which stimulates PKA-dependent ERK signalling. This is crucial to blood vessel growth as 'redox-dead' Cys17Ser RIα knock-in mice fully resistant to PKA disulphide-activation have deficient angiogenesis in models of hind limb ischaemia and tumour-implant growth. Disulphide-activation of PKA represents a new therapeutic target in diseases with aberrant angiogenesis.

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